Streptococcus equi has been known for a long time to be the cause of an acute disease of the upper respiratory tract in horses (Sweeney et al., Compendium Equine 9: 689-693 (1987)) This highly contagious disease is characterised by fever, mucopurulent nasal discharge, lymphadenopathy and subsequent abscessation of the lymph nodes of the head and the neck (Sweeney et al., Compendium Equine 9: 845-851 (1987)). The swelling of the lymph nodes is often so severe that the airways become obstructed. This phenomenon explains the common name of the disease; strangles.
The disease is only fatal in a minority of the cases, as described by Sigmund (Sigmund, O. H. and Fraser, C. M. eds.: The Merck Veterinary Manual, 5.sup.th Ed. Merck and Company Inc., Rahway, N.J.: 313-315 (1979)). Contrary to this, morbidity is generally high, and can be as high as 100% in susceptible populations.
Vaccines against the disease have also been known for a long time (Bazely, P. L.; Austr. Vet. J. 16: 243 (1940)) and (Bazely, P. L.; Austr. Vet. J. 18: 141-155 (1942). Until recently, only two kinds of vaccines were available: a) vaccines based on classical bacterins and b) subunit vaccines based on the M protein, an immunogenic protein. Both kinds of vaccine have their own severe drawbacks. Bacterins are notorious for their adverse reactions and are known to provide relatively little protection (Subcommittee on the Efficacy of Strangles Bacterin, Report, American Association of Equine Practitioners). Srivastava and Barnum (Can. J. Comp. Med. 45: 20-25 (1981)) demonstrated that commercial and autologous killed whole cell vaccines are not capable of inducing a sufficient level of antibodies to protect against strangles.
Woolcock Austr. Vet. J. 51: 554-559 (1975) showed that a vaccination scheme of three doses at ten day intervals is essential to obtain at least partial protection. Boschwitz comes to the conclusion for the major immunogenic subunit of S. equi, the M protein, that antibodies against this antigen are not sufficient to protect horses from natural or experimental infections (Cornell Vet. 81: 25-36 (1991)).
In a comparative study, in which both whole cell and M subunit vaccines were compared, Srivastava and Barnum, Can. J. Comp. Med. 49: 351-356 (1981) again reported the very weak results with these kinds of vaccines: repeated booster vaccinations are necessary to obtain reasonable antibody titres and the longevity of the high titres is short. Further booster vaccinations should be given at least once a year (Sweeney et al., Compendium Equine 9: 845-851 (1987)). Moreover, there is hardly any correlation between antibody titers and protection. Even recent papers, in which killed S. equi was administered intraperitoneally or orally describe only partial protection against challenge with live Streptococcus equi (Wallace et al, Vet. Immunol. and Immunopath. 48: 139-154 (1995). Classical vaccines based on bacterins or subunits are e.g. available trough Forth Dodge Laboratories, Coopers Animal Health and the Mobay Company (U.S. Pat. No. 4,944,942).
Mounting evidence in the literature indicates that immunity to S. equi is local, rather than systemic. The paramount importance of local immunity in conferring protection against streptococcal infection is i.a. well-documented by Bessen and Fischeffi, in J. Exp. Medicine 167: 1945-1950 (1988), and in Infect. and Immun. 56: 2555-2672 (1988)). It has been established that local immunity is mediated by mucosal antibodies as was summarised i.a. by Bernadette (J. Gen. Microbiol. 137:2125-2133 (1991).
And since the nasopharynx is the natural port of entrance for Streptococcus equi, it is now generally accepted that successful vaccination necessarily requires stimulation of the nasopharyngial immune response. (Galan et al., Inf. Immun. 47: 623-628 (1985), (Galan et al., Inf. Immun. 54: 202-206 (1986), (Timoney et al., In Kimura, y., Kotami, S., Shiokawa, y. (ed.). Recent advances in streptococci and streptococcal diseases. Reed Books, Danbury, N.H.).
The well-established importance of direct stimulation of the nasopharyngial immune response has contributed greatly to the current opinion, that only the intranasal application of a vaccine can provide at least partial protection.
A general problem with intranasally given live attenuated vaccines is the fact that the vaccine does not stay in the nose, but leaks away through sneezing, leaking and the like. This is an unwanted situation for two reasons: most of the vaccine virus becomes spread into the environment, and an overdose must be give to assure a sufficient level of vaccination. These disadvantages are however accepted in practice since as motivated above intranasal vaccination is currently considered the only way to obtain at least partial protection.
A live attenuated strain has to our knowledge only been described in WO/87/00436. In this application it is once more stated that intranasal/oral vaccination with live Streptococcus equi is the only way to obtain possible protection, since other routes of vaccination and/or the use of subunit vaccines are known to be ineffective. The disadvantage of this vaccine, however, is, that it is a non-encapsulated mutant. Therefore, no immune response against the lipopolysaccharide moiety of the bacterium is obtained.